title: PAX4 has the potential to function as a tumor suppressor in human melanoma.
abstract: We hypothesize that dysregulated expression levels of the developmental regulatory genes in the adult body result in tumor development and malignant progression. PAX genes discovered as human orthologous genes of Drosophila 'paired' encode transcription factors, which control the expression of target genes to go on along the program of development. In this study, we first quantified expression of 9 PAX genes in human nevus pigmentosus tissues, melanoma tissues and melanoma cell lines by the real-time reverse transcription-PCR method. As a result, we found that the expression levels of PAX4 and PAX9 were extremely low in melanoma tissues and cell lines compared to nevus pigmentosus tissues. We then established melanoma cells overexpressing PAX4 and examined roles of PAX4 in cell growth. PAX4-overexpression reduced in vitro cell growth of human melanoma C8161 and MeWo cells. BrdU-uptake assay and cell cycle analysis by flow cytometry indicated that the retardation of cell proliferation by PAX4-overexpression was due to decreased DNA synthesis and cell cycle arrest at the G0/G1 phase. Furthermore, treatment of C8161 and MeWo cells with 5-azacytidine, a DNA demethylating agent, induced the expression of PAX4, suggesting that DNA methylation repressed the PAX4 gene expression in human melanoma. These results suggest that PAX4 functions as a potent tumor suppressor.
authors.affiliation: Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hata
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Taichi
authors.initials: T
authors.lastname: Murai
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Arata
authors.initials: A
authors.lastname: Tsutsumida
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Moriuchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation / Q000187:drug effects; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D001374:Azacitidine